In the treatment of various cancers, chemotherapy is considered to be an effective therapeutic option. However, chemotherapeutic agents generally lack targeting specificity due to their inability to differentiate between normal or benign and malignant neoplasms undergoing rapid cellular division. As a consequence, these agents have significant normal tissue toxicity that include, but are not limited to, decreased erythrocyte, leukocyte, and platelet counts, nausea, vomiting, hair loss, and fatigue.
To maximize the prognostic outcomes in cancer patients, an optimal chemotherapeutic agent, in which the therapeutic ratio (tumor cell kill/normal tissue sparing) is very high, needs to be used. As known in the art, the selection of an optimal agent is based on a search to balance a marked growth-inhibitory or controlling effect on the cancer cell with the toxic effect on the host. While agent optimization is a complex process of basic science, research, and discovery involving cell biologists, chemists, pharmacologists, and physicians, a practical clinical approach is to develop methods that can more rapidly evaluate treatment efficacy following chemotherapy administration. Early identification of a poor responder allows the treatment to be modified, which can increase the potential for improved outcomes in these patients.
Thus, it is very important to monitor tumor response early in a chemotherapy process to identify and optimize the use of the chemotherapeutic agent for individual patients. Traditionally, monitoring has involved analysis of response by volumetric assessment, which is performed by evaluating changes in the tumor volume by direct physical or imaging-based measurement. Unfortunately, this process has an inherent latency due to the delay between chemotherapy administration and detection of gross tumor change during which time the therapeutic ratio might be reduced by non-specific targeting of the chemotherapy to rapidly dividing normal tissues, such as those within the oral cavities and hair.
As a specific example, there is evidence within patients with lymphoma to indicate that early response to chemotherapy, as measured by positron emission tomography (PET), using F-18 Fluorodeoxygluocose, is strongly correlated with improved treatment outcome. PET imaging is typically performed before initiation of chemotherapy to establish a metabolic baseline for the tumor and to provide a measure of overall size (i.e. volume). A second scan is performed after the administration of chemotherapy to assess treatment efficacy. However, this “early” assessment of treatment response is typically performed after two cycles of chemotherapy, typically six weeks following initiation of treatment. Unfortunately, the four to six week interval that normally applies for FDG-PET monitoring of tumor response presents a substantial impediment to effectively identifying non responders. Thus, the standard method of assessing response to chemotherapy is through the use of PET; however, this method is typically performed after two cycles of chemotherapy, during which time significant normal tissue toxicity is commonly observed.
Therefore, it would be desirable to have a system and method to test the effectiveness of chemotherapy administered to a patient as early as possible, while still differentiating between responders and non-responders. Such systems and methods enabling the early identification of poor responders allows for earlier treatment modification, thereby increasing the potential for improved outcomes in these patients.